ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6022+5G>A (rs376389213)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208243 SCV000264184 uncertain significance Heart disease 2015-05-21 criteria provided, single submitter clinical testing
Invitae RCV000461824 SCV000541713 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2020-01-13 criteria provided, single submitter clinical testing This sequence change falls in intron 39 of the RYR2 gene. It does not directly change the encoded amino acid sequence of the RYR2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs376389213, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 222789). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000621730 SCV000736487 uncertain significance Cardiovascular phenotype 2018-09-29 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV001097375 SCV001253652 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001097376 SCV001253653 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color RCV001182247 SCV001347635 uncertain significance Cardiomyopathy 2020-02-19 criteria provided, single submitter clinical testing

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